Overview
46,XY difference of sex development (DSD) of endocrine origin is a condition where a person has male chromosomes (46,XY) but their body does not develop typical male physical features due to problems with hormone production or hormone action during development. Normally, a baby with XY chromosomes produces hormones like testosterone and anti-Müllerian hormone that guide the body to develop male reproductive organs. In this condition, something goes wrong in the hormonal pathway — either the body does not make enough of these hormones, or the body cannot respond to them properly. This can result in a wide range of physical differences, from ambiguous genitalia (genitals that do not look clearly male or female) at birth, to a more female-typical appearance despite having XY chromosomes, to mild differences such as undescended testes or a small penis. Some individuals may not be diagnosed until puberty, when expected changes like voice deepening or facial hair growth do not occur. The specific cause can involve problems with enzymes needed to make testosterone (such as 5-alpha reductase deficiency or 17-beta hydroxysteroid dehydrogenase deficiency), issues with the adrenal glands, or problems with how cells respond to androgens (male hormones). Treatment depends on the underlying cause and may include hormone replacement therapy, surgical options, and psychological support. A team of specialists works together to provide individualized care based on each person's needs and identity.
Key symptoms:
Ambiguous genitalia at birthGenitals that appear more female despite having XY chromosomesUndescended testes (testes that have not moved into the scrotum)Small penis (micropenis)Opening of the urethra on the underside of the penis (hypospadias)Lack of expected puberty changes in boysBreast development at puberty in someone raised as maleAbsent or irregular menstrual periods in someone raised as femaleInfertility or reduced fertilityInguinal hernia containing a gonadLack of facial or body hair developmentDifferences in internal reproductive organsPsychological distress related to body differences
Variable
Can be inherited in different ways depending on the underlying gene
Neonatal
Begins at or shortly after birth (first 4 weeks)
Treatments
No FDA-approved treatments are currently listed for 46,XY difference of sex development of endocrine origin.
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Specialists
View all specialists →No specialists are currently listed for 46,XY difference of sex development of endocrine origin.
Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
Travel Grants
No travel grants are currently matched to 46,XY difference of sex development of endocrine origin.
Community
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Caregiver Resources
NORD Caregiver Resources
Support, advocacy, and financial assistance for caregivers of rare disease patients.
Mental Health Support
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Family & Caregiver Grants
Financial assistance programs specifically for caregivers of rare disease patients.
Social Security Disability
Learn how rare disease patients may qualify for SSDI/SSI benefits.
Questions for your doctor
Bring these to your next appointment
- Q1.What is the specific cause of my child's (or my) condition, and has genetic testing confirmed it?,What hormone treatments are recommended, and what are the long-term effects?,Is there a risk of gonadal tumors, and how will this be monitored?,What are the options regarding surgery, and can any decisions be safely delayed?,What psychological support services are available for our family?,What does this mean for future fertility, and are there options to preserve fertility?,How should we talk to our child about their condition as they grow up?
Common questions about 46,XY difference of sex development of endocrine origin
What is 46,XY difference of sex development of endocrine origin?
46,XY difference of sex development (DSD) of endocrine origin is a condition where a person has male chromosomes (46,XY) but their body does not develop typical male physical features due to problems with hormone production or hormone action during development. Normally, a baby with XY chromosomes produces hormones like testosterone and anti-Müllerian hormone that guide the body to develop male reproductive organs. In this condition, something goes wrong in the hormonal pathway — either the body does not make enough of these hormones, or the body cannot respond to them properly. This can resul
At what age does 46,XY difference of sex development of endocrine origin typically begin?
Typical onset of 46,XY difference of sex development of endocrine origin is neonatal. Age of onset can vary across affected individuals.